Since 1967 when van Wezel introduced and demonstrated the use of small globular particles as support for growth of anchorage-dependent cells in suspended cultures, a variety of composite materials and microspheres have been used in 3-dimensional (3D) cell cultures. They include dextran microspheres, polystyrene microspheres, polyacrylamide microspheres, and silica glass beads to name a few. Microcarriers made from degradable polymers have found applications in sustained delivery of drugs or other biologically active compounds (Uchida et al. 1997. Chem. Pharm. Bull. 45:1539-1543; Wakiyama et al. 1982. Chem. Pharm. Bull. 30:3719-3727; Mathiowitz et al. 1988. J. Appl. Polym. Sci. 35:755-774; Mathiowitz et al. 1990. Polymer 31:547-555; Albertson et al. 1996. J. Appl. Polym. Sci. 62:695-705).
Calcium phosphate-based ceramics and glasses have the ability to bond with bone tissues and have been widely used in bone repair (Ducheyne, P. and J. Lemons. 1988. Ann. NY Acad. Sci. 523). Based on a comparison of literature data it was suggested that 45S5 "bioactive" glass (45% SiO.sub.2, 24.5% Na.sub.2 O, 24.5% CaO, and 6% P.sub.2 O.sub.5) had the highest rate of bonding to bone (Hench, L.L. 1988. Ann. NY Acad. Sci. 523:54-71), where "bioactive" means the material has the ability to interact or bind to living tissue. Recently, 45S5 bioactive glass has been considered for use as bioactive ceramic microspheres in 3D bone cell cultures in rotating bioreactors (Qiu et al. 1998. Tissue Engineer. 4:19-34). The use of bone bioactive materials is of great interest in bone synthesis in vitro because of their ability to promote cell-material bonding and the potential to enhance bone formation.
It is believed that the presence and formation of calcium hydroxyapatite at the implant-bone interface is critical for bone bonding and is one of the key features necessary for successful bioactive bone implants. Calcium hydroxyapatite coatings on implants or calcium hydroxyapatite blocks have been used to produce implants with bone-binding abilities. Through use of an in vitro immersion method using a simulated physiological solution, a solution that mimics the ion concentration in body fluids, the formation of the calcium hydroxyapatite layers on bioactive glasses, bioactive glass-ceramics and polymers have been produced and this method of "in vitro immersion" used to predict bone-bonding potential of bone implant materials (Kokubo et al. 1990. J. Biomed. Mater. Res. 24:721-734; Li et al. 1997. J. Biomed. Mater. Res. 34:79-86).
Solid bioceramic microspheres typically have a density higher than 2 g/cm.sup.3. When they are used in bioreactors, the solid ceramic microspheres experience a high shear stress which causes cell detachment and damage (Qiu et al. 1998. Tissue Engineer. 4:19-34). This problem has been solved by reducing the apparent density of the microspheres through a hollow structure approach (Qiu et al. 1999. Biomaterials 20:989-1001). Cell culture studies have confirmed that the hollow bioceramic microspheres (SiO.sub.2 /Al.sub.2 O.sub.3 /CaP) experience a low shear stress and can support 3D bone cell cultures in rotating bioreactors. However, because of their non-degradable component, Al.sub.2 O.sub.3, hollow bioceramic microspheres cannot be completely replaced by bone tissues. New microcarriers that are bioactive, degradable and with a density low enough to produce a low shear stress, are desired.
A new bioactive and degradable composite material has been developed for use in 3-dimensional bone tissue engineering and bone implant materials.